A model of chromatin-dependent DNA replication sequences based on the decondensation units hypothesis

Abstract

A model of chromatin-dependent DNA replication sequences was developed on the previously reported "decondensation units" hypothesis and its kinetic properties were examined by way of calculating various numerical indices using a Monte Carlo procedure. The model has much in common with the previous one but a fundamental difference is that the unit is assumed to consist of linearly arranged H-, D-, A- and S-zones each containing genes of different functional categories which are called H-, D-, A- and S-genes, respectively. The units are decondensed by the action of D-factors, i.e. decondensation factors, from H-zone to the end of S-zone and the genes in decondensed regions release signals to produce housekeeping enzymes, D-factors, A-factors and S-factors. These products are stored and at the same time degraded. A-factors activate replication origins in the decondensed regions and S-factors induce DNA synthesis at the activated origins. Replicated DNA is recondensed and gene activities are shut down in the recondensed chromatin. The factors are produced under the control of chromosome cycle and in turn affect chromosomes. Thus, dual control mechanism operates as Mazia and Prescott have argued. Biochemical and cytogenetic basis of this model was reviewed briefly and some results of simulation presented which include DNA synthesis rate vs. DNA content relationships. An outstanding characteristic of the model is the constancy of cellular state in A-subphase located in the late G1.